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Current Bioinformatics

Author(s): Maria A. Zelenova and Ivan Y. Iourov*

DOI: 10.2174/1574893617666220907121155

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Possibilities and Limitations of CNV Interpretation Software and Algorithms in Homo Sapiens

Page: [883 - 887] Pages: 5

  • * (Excluding Mailing and Handling)

Abstract

Background: Technical advances and cost reduction have allowed for the worldwide popularity of array platforms. Otherwise called “molecular karyotyping”, it yields a large amount of CNV data, which is useless without interpretation.

Objective: This study aims to review existing CNV interpretation software and algorithms to reveal their possibilities and limitations.

Results: Open and user-friendly CNV interpretation software is limited to several options, which mostly do not allow for cross-interpretation. Many algorithms are generally based on the Database of Genomic Variants, CNV size, inheritance data, and disease databases, which currently seem insufficient.

Conclusion: The analysis of CNV interpretation software and algorithms resulted in a conclusion that it is necessary to expand the existing algorithms of CNV interpretation and at least include pathway and expression data. A user-friendly freely available CNV interpretation software, based on the expanded algorithms, is yet to be created.

Keywords: SNP array, CNV interpretation, bioinformatics, genetics, brain diseases

Graphical Abstract

[1]
Pös O, Radvanszky J, Styk J, et al. Copy number variation: Methods and clinical applications. Appl Sci (Basel) 2021; 11(2): 819.
[http://dx.doi.org/10.3390/app11020819]
[2]
Magini P, Scarano E, Donati I, et al. Challenges in the clinical interpretation of small de novo copy number variants in neurodevelopmental disorders. Gene 2019; 706: 162-71.
[http://dx.doi.org/10.1016/j.gene.2019.05.007] [PMID: 31085274]
[3]
Requena F, Abdallah HH, García A, et al. CNVxplorer: A web tool to assist clinical interpretation of CNVs in rare disease patients. Nucleic Acids Res 2021; 49(W1): W93-W103.
[http://dx.doi.org/10.1093/nar/gkab347] [PMID: 34019647]
[4]
Spector JD, Wiita AP. A guide to using ClinTAD for interpretation of DNA copy number variants in the context of topologically associated domains. Curr Protoc Hum Genet 2020; 108(1): e106.
[http://dx.doi.org/10.1002/cphg.106] [PMID: 33170544]
[5]
McLaren W, Gil L, Hunt SE, et al. The ensembl variant effect predictor. Genome Biol 2016; 17(1): 122.
[http://dx.doi.org/10.1186/s13059-016-0974-4] [PMID: 27268795]
[6]
Geoffroy V, Herenger Y, Kress A, et al. AnnotSV: An integrated tool for structural variations annotation. Bioinformatics 2018; 34(20): 3572-4.
[http://dx.doi.org/10.1093/bioinformatics/bty304] [PMID: 29669011]
[7]
Lupiáñez DG, Kraft K, Heinrich V, et al. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell 2015; 161(5): 1012-25.
[http://dx.doi.org/10.1016/j.cell.2015.04.004] [PMID: 25959774]
[8]
Franke M, Ibrahim DM, Andrey G, et al. Formation of new chromatin domains determines pathogenicity of genomic duplications. Nature 2016; 538(7624): 265-9.
[http://dx.doi.org/10.1038/nature19800] [PMID: 27706140]
[9]
Buysse K, Delle Chiaie B, Van Coster R, et al. Challenges for CNV interpretation in clinical molecular karyotyping: Lessons learned from a 1001 sample experience. Eur J Med Genet 2009; 52(6): 398-403.
[http://dx.doi.org/10.1016/j.ejmg.2009.09.002] [PMID: 19765681]
[10]
Riggs ER, Andersen EF, Cherry AM, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med 2020; 22(2): 245-57.
[http://dx.doi.org/10.1038/s41436-019-0686-8] [PMID: 31690835]
[11]
Iourov IY, Vorsanova SG, Yurov YB, et al. The cytogenomic “theory of everything”: Chromohelkosis may underlie chromosomal instability and mosaicism in disease and aging. Int J Mol Sci 2020; 21(21): 8328.
[http://dx.doi.org/10.3390/ijms21218328] [PMID: 33171981]
[12]
Iourov IY, Vorsanova SG, Yurov YB. In silico molecular cytogenetics: A bioinformatic approach to prioritization of candidate genes and copy number variations for basic and clinical genome research. Mol Cytogenet 2014; 7(1): 98.
[http://dx.doi.org/10.1186/s13039-014-0098-z] [PMID: 25525469]
[13]
Iourov IY, Vorsanova SG, Korostelev SA, Zelenova MA, Yurov YB. Long contiguous stretches of homozygosity spanning shortly the imprinted loci are associated with intellectual disability, autism and/or epilepsy. Mol Cytogenet 2015; 8(1): 77.
[http://dx.doi.org/10.1186/s13039-015-0182-z] [PMID: 26478745]
[14]
Ceballos FC, Joshi PK, Clark DW, Ramsay M, Wilson JF. Runs of homozygosity: Windows into population history and trait architecture. Nat Rev Genet 2018; 19(4): 220-34.
[http://dx.doi.org/10.1038/nrg.2017.109] [PMID: 29335644]
[15]
Szpiech ZA, Mak ACY, White MJ, et al. Ancestry-dependent enrichment of deleterious homozygotes in runs of homozygosity. Am J Hum Genet 2019; 105(4): 747-62.
[http://dx.doi.org/10.1016/j.ajhg.2019.08.011] [PMID: 31543216]
[16]
Iourov IY, Vorsanova SG, Yurov YB. The variome concept: Focus on CNVariome. Mol Cytogenet 2019; 12(1): 52.
[http://dx.doi.org/10.1186/s13039-019-0467-8] [PMID: 31890032]
[17]
Wyandt HE, Wilson GN, Tonk VS. Human chromosome variation: Heteromorphism, polymorphism and pathogenesis. Springer Singapore 2017; pp. 235-417.
[http://dx.doi.org/10.1007/978-981-10-3035-2_10]
[18]
Zelenova MA, Yurov YB, Vorsanova SG, Iourov IY. Laundering CNV data for candidate process prioritization in brain disorders. Mol Cytogenet 2019; 12(1): 54.
[http://dx.doi.org/10.1186/s13039-019-0468-7] [PMID: 31890034]
[19]
Nowakowska B. Clinical interpretation of copy number variants in the human genome. J Appl Genet 2017; 58(4): 449-57.
[http://dx.doi.org/10.1007/s13353-017-0407-4] [PMID: 28963714]
[20]
Khelifa HB, Soyah N, Labalme A, et al. Genomic microarray in intellectual disability: The usefulness of existing systems in the interpretation of copy number variation. J Pediatr Genet 2017; 6(02): 084-91.
[21]
Hollenbeck D, Williams CL, Drazba K, et al. Clinical relevance of small copy-number variants in chromosomal microarray clinical testing. Genet Med 2017; 19(4): 377-85.
[http://dx.doi.org/10.1038/gim.2016.132] [PMID: 27632688]
[22]
Vermeesch JR, Brady PD, Sanlaville D, Kok K, Hastings RJ. Genome-wide arrays: Quality criteria and platforms to be used in routine diagnostics. Hum Mutat 2012; 33(6): 906-15.
[http://dx.doi.org/10.1002/humu.22076] [PMID: 22415865]
[23]
Ghulam A, Lei X, Guo M, Bian C. Comprehensive analysis of features and annotations of pathway databases. Curr Bioinform 2021; 15(8): 803-20.
[http://dx.doi.org/10.2174/1574893615999200413123352]
[24]
Iourov IY, Vorsanova SG, Yurov YB. Pathway-based classification of genetic diseases. Mol Cytogenet 2019; 12(1): 4.
[http://dx.doi.org/10.1186/s13039-019-0418-4] [PMID: 30766616]
[25]
Iourov IY, Vorsanova SG, Voinova VY, Yurov YB. 3p22.1p21.31 microdeletion identifies CCK as Asperger syndrome candidate gene and shows the way for therapeutic strategies in chromosome imbalances. Mol Cytogenet 2015; 8(1): 82.
[http://dx.doi.org/10.1186/s13039-015-0185-9] [PMID: 26523151]